Accumulation of Boron in Human Malignant Glioma Cells in vitro is Cell Type Dependent

Abstract

It has been shown that human malignant glioma tumours consist of several subpopulations of tumour cells. Due to heterogeneity and different degrees of vascularisation cell subpopulations possess varying resistance to chemo- or radiation therapy. Therefore, therapy is dependent on the ability to specifically target a tumour cell. Boron neutron capture therapy (BNCT) is a bimodal method, in radiation therapy, taking advantage of the ability of the stable isotope boron-10 to capture neutrons. It results in disintegration products depositing large amounts of energy within a short length, approximately one cell diameter. Thereby, selective irradiation of a target cell may be accomplished if a sufficient amount of boron has been accumulated and hence the cell-associated boron concentration is of critical importance. The accumulation of boron, boronophenylalanine (BPA), was investigated in two human glioma cell subpopulations and a human fibroblast cell line in vitro. The cells were incubated at low boron concentrations (0-5 microg B/ml). Oil filtration was then used for separation of extracellular and cell-associated boron. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) was used for boron determination. Significant (P < 0.05) differences in accumulation ratio (relation between cell-associated and extracellular boron concentration) between human malignant glioma cell lines were found. Human fibroblasts, used to represent normal cells, showed a growth-dependent uptake and a lower accumulation ratio than the glioma cells. Our findings indicate that BPA concentration, incubation time and differences in boron uptake between cell subpopulations should be considered in BNCT.

Boron neutron capture therapy induces apoptosis of glioma cells through Bcl-2/Bax

“…Typical apoptotic morphological changes were confirmed in U87, U251, and SHG44 cells after BNCT treatment, using transmission electron microscopy and Hoechst 33342 staining. Furthermore, previous studies have shown that BPA has no toxicity effect on cells at a dosage up to 110 μg [ 10 B]/ml [24]. Few apoptotic changes were apparent in nonirradiated control cells, showing, for the first time, that the pro-apoptotic effect of BNCT plays an important role in the reduction of cell proliferation.…”

Boron Neutron Capture Therapy of Cancer: Current Status and Future Prospects

“…First, there is a need for more selective and effective boron agents that, when used either alone or in combination, could deliver the requisite amounts (f20 Ag/g) of boron to the tumor. Furthermore, their delivery must be optimized to improve both tumor uptake and cellular microdistribution, especially to different subpopulations of tumor cells (196). Several studies have shown that there is considerable patient-to-patient as well i.t.…”

Microdistribution and quantification of the boron neutron capture therapy drug BPA in primary cell cultures of human glioblastoma tumour by NanoSIMS

“…8,10,40,41 In order to limit recurrence rates, crucial targets for BNCT are the neoplastic cells that infiltrate the normal tissues around the tumour core, so-called brain around tumour (BAT). 42 Previous studies have reported differential 10 B uptake in these cells, compared to the main tumour mass, depending on the duration of drug dosing. [43][44][45] It is therefore important to study the pharmacokinetics of 10 B uptake and distribution as this may influence the BNCT treatment regime.…”